Commonly owned copending U.S. patent application Ser. No. 630,938, filed July 16, 1984, now abandoned, describes two bovine bone-derived CIFs, designated CIF-A and CIF B. Both have molecular weights of approximately 26,000 daltons by SDS-PAGE and are dimers. They each exhibit in vitro chondrogenic activity by themselves, as measured by cartilage specific proteoglycan (PG) production in an agarose gel culture model using fetal rat mesenchymal cells. Neither, however, is chondrogenically active in vivo by itself. Amino acid sequencing of the CIF-A showed that it has a partial (30 amino acids) N-terminal sequence identical to that reported for a human placenta-derived polypeptide called beta-type transforming growth factor (TGF-.beta.). The partial N-terminal sequence of CIF-B is different from that of TGF-.beta.. Both CIFs exhibit activity in the TGF-.beta. assay (ability to induce anchorage-independent growth of normal rat kidney cell colonies in soft agar).
TGF-.beta. derived from bovine kidney, human placenta, and human platelets is described in International Patent Application PCT/US83/01460, published Mar. 29, 1984 under no. W084/01106, EPA 84450016.5, published Dec. 19, 1984 under no. 0128849, and U.S. Patent Applications Ser. Nos. 500,832, 500,833, and 500,927, filed June 3, 1983, all now abandoned. These applications present data showing that such TGF-.beta., when combined with EGF or TGF-.alpha., (1) promotes cell proliferation in the above mentioned soft agar culture assay and (2) promotes cell proliferation and protein deposition in a rat soft tissue wound healing model. The applications characterize the TGF-.beta.s as being dimers having a molecular weight of approximately 26,000 daltons by SDS-PAGE.